Obesity is a liability in cancer immunotherapy

Gaining an excessive amount of weight may lead to dangerous inflammation in response to anticancer treatment, according to a new study. Overweight mice were found to develop lethal inflammation in response to certain anticancer therapies. This suggests a possible link between body weight and adverse side effects in cancer patients treated with similar protocols.

Cancer treatment has been revolutionized by new approaches aimed at stimulating the body's own immune system to fight off tumor cells. These immunotherapy approaches have proven successful in many types of cancer, but they are also associated with dangerous inflammation in some patients.

This group of researchers from the University of California Davis led by William Murphy, PhD, had previously shown that treating mice with a combination of immune-activating stimuli, consisting of anti-CD40 antibodies and interleukin-2 (IL-2), stimulates tumor-fighting immune cells to eradicate cancer in young mice.

In old mice, however, the same treatment triggered deadly inflammation in this study. The treatment led to deadly cytokine storms in these mice. Like the old mice, mice that were young and obese succumbed to lethal inflammation from cytokine storms in response to treatment.

However, in mice with less visceral fat due to calorie restriction (dieting), depleting macrophages, or blockading tumor necrosis factor in conjunction with the treatment prevented the cytokine storms and protected them from lethality.

As with humans, mice often accumulate fat as they age. The current study, published in The Journal of Experimental Medicine (2014; doi:10.1084/jem.20140116), now finds that lethal inflammation in response to anti-CD40/IL-2 immunotherapy is determined more by fat than age.

The study suggests that the results of preclinical immunotherapy studies in mice and humans, which are primarily performed on young subjects, should be interpreted with caution, particularly as cancer is a disease that predominately affects the elderly.

“Adiposity is a critical factor in the age-associated pathological responses to systemic anticancer immunotherapy,” wrote the authors.